0 8 TNFalpha TNFalpha NNP 9 19 cooperates cooperate VBZ 20 24 with with IN 25 28 the the DT 29 36 protein protein NN 37 43 kinase kinase NNP 44 45 A a NN 46 53 pathway pathway NN 54 56 to to TO 57 72 synergistically synergistically RB 73 81 increase increase VB 82 87 HIV-1 HIV-1 NNP 88 91 LTR LTR NNP 92 105 transcription transcription NN 106 109 via via IN 110 120 downstream downstream JJ 121 129 TRE-like tre-like JJ 130 134 cAMP camp NN 135 143 response response NN 144 152 elements element NNS 152 153 . . . 155 165 Activating activate VBG 166 175 protein-1 protein-1 NN 176 177 ( ( ( 177 181 AP-1 ap-1 NN 181 182 ) ) ) 183 190 binding binding NN 191 194 TPA TPA NNP 195 205 responsive responsive JJ 206 214 elements element NNS 215 216 ( ( ( 216 219 TRE TRE NNP 219 220 ) ) ) 221 224 are be VBP 225 232 located located JJ 233 243 downstream downstream RB 244 246 of of IN 247 250 the the DT 251 264 transcription transcription NN 265 275 initiation initiation NN 276 280 site site NN 281 283 in in IN 284 287 the the DT 288 290 U5 u5 NN 291 297 region region NN 298 300 of of IN 301 304 the the DT 305 310 HIV-1 HIV-1 NNP 311 315 long long JJ 316 324 terminal terminal JJ 325 331 repeat repeat NN 332 333 ( ( ( 333 336 LTR LTR NNP 336 337 ) ) ) 337 338 . . . 339 344 These these DT 345 355 downstream downstream JJ 356 364 sequence sequence NN 365 373 elements element NNS 373 374 , , , 375 381 termed term VBN 382 385 DSE DSE NNP 385 386 , , , 387 390 can can MD 391 395 bind bind VB 396 400 both both CC 401 405 AP-1 ap-1 NN 406 409 and and CC 410 418 CREB/ATF CREB/ATF NNP 419 432 transcription transcription NN 433 440 factors factor NNS 440 441 . . . 442 450 Recently recently RB 450 451 , , , 452 454 we we PRP 455 467 demonstrated demonstrate VBD 468 472 that that IN 473 476 the the DT 477 480 DSE DSE NNP 481 484 are be VBP 485 489 also also RB 490 505 cAMP-responsive camp-responsive JJ 506 514 elements element NNS 515 516 ( ( ( 516 519 CRE CRE NNP 519 520 ) ) ) 520 521 , , , 522 527 since since IN 528 532 they they PRP 533 541 mediated mediate VBD 542 552 activation activation NN 553 560 signals signal NNS 561 569 elicited elicit VBN 570 572 by by IN 573 580 cholera cholera NN 581 586 toxin toxin NN 587 588 ( ( ( 588 591 Ctx Ctx NNP 591 592 ) ) ) 592 593 , , , 594 595 a a DT 596 602 potent potent JJ 603 612 activator activator NN 613 615 of of IN 616 619 the the DT 620 634 cAMP-dependent camp-dependent JJ 635 642 protein protein NN 643 649 kinase kinase NNP 650 651 A A NNP 652 653 ( ( ( 653 656 PKA PKA NNP 656 657 ) ) ) 658 664 signal signal NN 665 677 transduction transduction NN 678 685 pathway pathway NN 685 686 . . . 687 689 In in IN 690 693 the the DT 694 701 present present JJ 702 707 study study NN 707 708 , , , 709 711 we we PRP 712 723 demonstrate demonstrate VBP 724 728 that that IN 729 732 the the DT 733 738 HIV-1 HIV-1 NNP 739 742 DSE DSE NNP 743 746 can can MD 747 754 mediate mediate VB 755 758 the the DT 759 774 transcriptional transcriptional JJ 775 782 synergy synergy NN 783 791 elicited elicit VBN 792 794 by by IN 795 798 the the DT 799 810 combination combination NN 811 813 of of IN 814 817 Ctx Ctx NNP 818 821 and and CC 822 830 TNFalpha TNFalpha NNP 830 831 . . . 832 835 Ctx Ctx NNP 836 844 combined combine VBN 845 849 with with IN 850 858 TNFalpha TNFalpha NNP 859 861 or or CC 862 870 IL-1beta IL-1beta NNP 871 873 to to TO 874 881 produce produce VB 882 883 a a DT 884 895 synergistic synergistic JJ 896 904 increase increase NN 905 907 in in IN 908 911 p24 p24 NN 912 919 antigen antigen NN 920 930 production production NN 931 933 in in IN 934 936 U1 u1 NN 937 949 promonocytic promonocytic JJ 950 955 cells cell NNS 955 956 . . . 957 969 Transfection transfection NN 970 977 studies study NNS 978 980 of of IN 981 984 LTR LTR NNP 985 993 reporter reporter NN 994 1004 constructs construct NNS 1005 1014 indicated indicate VBD 1015 1019 that that IN 1020 1028 mutation mutation NN 1029 1031 of of IN 1032 1035 the the DT 1036 1039 DSE dse NN 1040 1045 sites site NNS 1046 1055 abrogated abrogate VBD 1056 1059 the the DT 1060 1072 LTR-mediated ltr-mediated JJ 1073 1080 synergy synergy NN 1081 1088 induced induce VBN 1089 1091 by by IN 1092 1095 Ctx Ctx NNP 1096 1099 and and CC 1100 1108 TNFalpha TNFalpha NNP 1108 1109 , , , 1110 1117 whereas whereas IN 1118 1121 the the DT 1122 1129 synergy synergy NN 1130 1137 induced induce VBN 1138 1140 by by IN 1141 1144 Ctx Ctx NNP 1145 1148 and and CC 1149 1157 IL-1beta IL-1beta NNP 1158 1161 was be VBD 1162 1172 unaffected unaffected JJ 1172 1173 , , , 1174 1184 suggesting suggest VBG 1185 1193 TNFalpha TNFalpha NNP 1194 1197 and and CC 1198 1206 IL-1beta IL-1beta NNP 1207 1216 cooperate cooperate VBP 1217 1228 differently differently RB 1229 1233 with with IN 1234 1237 the the DT 1238 1246 cAMP/PKA camp/pka NN 1247 1257 activation activation NN 1258 1265 pathway pathway NN 1266 1268 to to TO 1269 1275 induce induce VB 1276 1281 HIV-1 HIV-1 NNP 1282 1292 expression expression NN 1293 1295 in in IN 1296 1298 U1 u1 NN 1299 1304 cells cell NNS 1304 1305 . . . 1306 1313 Because because IN 1314 1317 the the DT 1318 1321 DSE DSE NNP 1322 1325 are be VBP 1326 1330 also also RB 1331 1334 TRE tre NN 1335 1340 sites site NNS 1340 1341 , , , 1342 1344 we we PRP 1345 1353 assessed assess VBD 1354 1357 the the DT 1358 1364 effect effect NN 1365 1367 of of IN 1368 1371 the the DT 1372 1379 agonist agonist NN 1380 1392 combinations combination NNS 1393 1395 on on IN 1396 1410 AP-1-dependent ap-1-dependent JJ 1411 1424 transcription transcription NN 1424 1425 . . . 1426 1434 TNFalpha TNFalpha NNP 1435 1437 as as RB 1438 1442 well well RB 1443 1445 as as IN 1446 1454 IL-1beta IL-1beta NNP 1455 1465 cooperated cooperate VBD 1466 1470 with with IN 1471 1474 Ctx Ctx NNP 1475 1477 to to TO 1478 1485 produce produce VB 1486 1487 a a DT 1488 1499 synergistic synergistic JJ 1500 1510 activation activation NN 1511 1513 of of IN 1514 1527 AP-1-mediated ap-1-mediated JJ 1528 1541 transcription transcription NN 1541 1542 . . . 1543 1548 These these DT 1549 1553 data datum NNS 1554 1562 indicate indicate VBP 1563 1567 that that IN 1568 1571 the the DT 1572 1580 TRE-like tre-like JJ 1581 1596 cAMP-responsive camp-responsive JJ 1597 1600 DSE dse NN 1601 1606 sites site NNS 1607 1613 within within IN 1614 1617 the the DT 1618 1633 5’-untranslated 5'-untranslated JJ 1634 1640 leader leader NN 1641 1644 can can MD 1645 1652 mediate mediate VB 1653 1656 the the DT 1657 1672 transcriptional transcriptional JJ 1673 1686 cooperativity cooperativity NN 1687 1694 between between IN 1695 1703 TNFalpha TNFalpha NNP 1704 1707 and and CC 1708 1711 the the DT 1712 1720 cAMP/PKA camp/pka NN 1721 1728 pathway pathway NN 1728 1729 . . . 1730 1735 Since since IN 1736 1739 the the DT 1740 1743 DSE DSE NNP 1744 1747 and and CC 1748 1751 TRE TRE NNP 1752 1757 sites site NNS 1758 1764 cannot cannot MD 1765 1769 bind bind VB 1770 1778 CREB/ATF creb/atf NN 1779 1789 homodimers homodimer NNS 1789 1790 , , , 1791 1793 we we PRP 1794 1801 propose propose VBP 1802 1803 a a DT 1804 1813 mechanism mechanism NN 1814 1816 in in IN 1817 1822 which which WDT 1823 1826 the the DT 1827 1832 HIV-1 HIV-1 NNP 1833 1836 DSE DSE NNP 1837 1841 bind bind VBP 1842 1854 heterodimers heterodimer NNS 1855 1863 composed compose VBN 1864 1866 of of IN 1867 1871 both both CC 1872 1876 AP-1 ap-1 NN 1877 1880 and and CC 1881 1889 CREB/ATF creb/atf NN 1890 1898 proteins protein NNS 1898 1899 . . . 1900 1909 Copyright Copyright NNP 1910 1914 1997 1997 CD 1915 1923 Academic Academic NNP 1924 1929 Press Press NNP 1929 1930 . . .